Studies with proline analogs, which selectively block collagen deposition and thus cause the production of a faulty basement membrane, have been found to cause a regression of mammary tumors that produce basement membranes. Similarly, normal mammary epithelium which also produces this extracellular matrix material is caused to involute by these proline analogs. These studies have suggested that production of basement membranes is important for the growth and survival of normal and neoplastic mammary epithelium. Consequently we have began a series of experiments to evaluate the mechanisms by which production of basement membrane collagen is controlled. The results indicate that at least 3 major mechanisms exist: (1) Modulation of collagen turnover which is suppressed by glucocorticoids (2) increased synthesis as a consequence of cell contact with "foreign" surfaces (3) increased synthesis in response to growth factors and hormones. In the latter category is a new class of growth factors which we have discovered. These are produced by and autostimulate mammary tumor cells to enhance their rate of collagen production. One such factor has been partially purified from rat, mouse and human mammary tumors and human milk. The human milk and human mammary tumor factors have the same PI and are probably identical. The rodent factors have a different PI. These factors differentially stimulate collagen synthesis by as much as 10 fold and are believed to be important in the growth control of mammary tumors. Further studies are underway to develop a radioimmuoassay for the factors for screening for their presence and possible function in mammary tumorigenesis.